tbuckley/cabot-search huggingface dataset:
Abstract 11524: Maternal Vaping Impacts on Cerebrovascular Function in Offspring
Authors: Amber Mills, Sydney Nassabeh, James Frazier, Derek Maloney, Paul D Chantler, Ivan M Olfert
Journal: Circulation (2022)

Electronic cigarettes (E-cigs) are marketed as a safer alternative to smoking even during pregnancy, but health effects of vaping are still largely unknown and under investigation. Emerging studies find cerebrovascular dysfunction in offspring with in-utero E-cig exposure, but little is known what the effect of E-cig device wattage has. We hypothesize maternal vaping at 30 watts will have a greater effect (compared to 5-watts) on cerebrovascular dysfunction in offspring. Female Sprague Dawley rats were time-mated, and the dams were randomly assigned to the following groups 1) 5-watts (N=5), 2) 30-watts (N=5), 3) and ambient air (control, N=5). Exposure was 60-puffs/day (5 days/week) beginning on gestational day (GD) 2-3 until GD21 using whole-body chambers. E-liquid was 50% vegetable glycerin, and 50% propylene glycol containing no nicotine and no flavor. One male &amp; female offspring per dam are reported at 1- and 6-months of age, where the middle cerebral artery (MCA) was isolated and reactivity assessed using dose-response (10 -9 M to 10 -4 M) to acetylcholine (ACh), serotonin (5-HT), and sodium nitroprusside (SNP) via pressure myography. 1-month offspring, maximal MCA dilation to ACh was impaired in both 5- and 30-watts compared to air (33±3%, 50±3%, respectively, p&lt;0.05). SNP-induced dilation (20±6%, 39±4%, respectively, p&lt;0.05) and 5-HT vasoconstriction (37±3%, 47±3%, respectively, p&lt;0.05) were blunted in both groups compared to controls. Compared to air, the 6-month offspring showed similar impairments in 5- and 30-watt groups (27±3% and 45±2%, respectively, p&lt;0.05). Likewise, SNP dilation (12±3% and 23±6%, p&lt;0.05) and 5-HT constriction (21±3% and 36±3%, p&lt;0.05) were impaired in 5- and 30-watt groups, respectively, compared to controls. For all conditions, 30-watt MCA impairment was significantly greater than 5-watts in 1 and 6-month offspring (p&lt;0.05). These data show (regardless of the E-cig device wattage used) that maternal vaping during pregnancy results in cerebrovascular impairment involving endothelial-dependent and -independent pathways in adolescent and adult offspring, but also shows that the magnitude of impairment is greater with maternal vaping at higher compared to lower wattage.
Abstract 12538: Intermittent Hypoxemia Progressively Destabilizes Ventricular Repolarization in Healthy Awake Subjects
Authors: Soroosh Solhjoo, Naresh M Punjabi, Trishul Siddharthan, Abigail L Koch, Ciprian M Crainiceanu, Mark C Haigney
Journal: Circulation (2022)

Introduction : Obstructive sleep apnea (OSA) is highly prevalent in the general population. OSA is associated with adverse cardiovascular events, including sudden cardiac death, but the mechanism is unclear. Intermittent hypoxemia, a pathognomonic feature of OSA, could increase the propensity for abnormal ventricular repolarization. We previously found that short-term exposure of awake healthy subjects to recurrent hypoxic episodes increased their heart rate (HR) and HR variability. Hypothesis: Exposure to intermittent hypoxia increases ventricular repolarization instability in awake healthy subjects. Methods: Healthy adults (N = 19) were exposed to either intermittent hypoxia or air for 4 hours on two different days in a randomized order. Intermittent hypoxia was induced with exposure to hypoxic gas (95% N 2 and 5% O 2 ) or ambient air in an alternative fashion at a frequency of ⁓ 25 times/hour, mimicking moderate to severe OSA. Repolarization stability was assessed using the QT variability index (QTVI), a validated predictor of cardiac arrhythmias and mortality. HR and QTVI were measured from one-lead ECG over consecutive 5-min epochs. Paired sample t - test was used to assess statistical associations. Results: Mean oxygen saturation levels were lower during exposure to intermittent hypoxia (90.86 ± 0.19%) versus normoxia (97.37 ± 0.20%, P &lt; 10 -13 ). Electrocardiographic measures at baseline were similar between the two conditions. No changes in these measures were noted during the conditions of normoxia. However, with intermittent hypoxia, mean HR and QTVI steadily increased (HR: 63.31 ± 1.51 initial, 69.21 ± 2.14 final, P &lt; 0.001; QTVI: -1.85 ± 0.04 initial, -1.64 ± 0.07 final, P = 0.016). By the end of the 4-hour experiment, QTVI was greater in hypoxia vs. normoxia (final QTVI in hypoxia: -1.64 ± 0.07, in normoxia: -1.86 ± 0.06, P = 0.021). Conclusion: Four hours of intermittent hypoxia in awake normal healthy subjects progressively destabilized ventricular repolarization. Chronic exposure to recurrent periods of intermittent hypoxemia in OSA can increase ventricular repolarization and contribute to the OSA-associated adverse cardiovascular events, including sudden cardiac death.
Abstract 12552: Causal Effect of Exposure to Elevated Lipoprotein(a) Levels on the Blood Transcriptome : A Mendelian Randomization Study
Authors: Jerome Bourgault, Benoit Arsenault
Journal: Circulation (2022)

INTRODUCTION: Lipoprotein(a) [Lp(a)] is one of the strongest genetic risk factors for atherosclerotic cardiovascular diseases (ASCVD). Several ex vivo studies have revealed a pro-inflammatory and pro-atherogenic role of Lp(a) in the etiology of ASCVD, mainly through induction of inflammation, metabolic processes, and apoptosis. However, whether Lp(a) causally influences the human transcriptome is unknown. Here, we aimed at identifying whether genetically-predicted Lp(a) levels could also affect the whole blood expression of genes involved in metabolic- and inflammatory-related pathways. Methods: We performed a series of inverse-variance weighted mendelian randomization analyses using single-nucleotide polymorphisms located in the LPA locus (±500kb; p&lt;5x10 -8 ) from the UK Biobank GWAS on Lipoprotein(a) quantiles as exposure (n=377,590 and whole blood expression levels of 14,288 coding gene from eQTLGen as outcomes (n=31,684 from 37 studies). We then used the Functional Mapping and Annotation of Genome-Wide Association Studies tool (FUMA) to identify gene sets for cardiometabolic- and inflammatory-related pathways from gene ontology biological processes. Results: The MR analyses identified 1363 genes that may be causally influenced by exposure to high Lp(a) levels (with p&lt;0.05). The 10 most strongly associated genes with genetically-predicted Lp(a) levels are FSTL3 , PRKC1 , PDE6C , PLXNB3 , SESN1 , SASH1 , CD1D , CCDC102A , SS18L1 and TCF12 . These genes are also differentially expressed in the heart. We identified 16 cardiometabolic-related pathways, mostly related to immune response, signaling, apoptosis, cardiovascular and vasculature development, cell proliferation, metabolic process, and catalytic activity. The 5 most significant pathways are regulation of cell population proliferation, regulation of intracellular signal transduction, positive regulation of cell population proliferation, cardiovascular system development and TOR signaling. Conclusions: Results of this study highlight a potentially causal effect of exposure to elevated Lp(a) levels on several key genes involved in metabolic processes and inflammation and provide mechanistic insight on the pathobiological role of Lp(a) in the etiology of ASCVD.
Abstract 11217: Pregnancy Outcomes in Unrepaired Congenital Heart Disease a Multicenter Experience From 1272 Patients
Authors: Qian Zhang, Zhu Fang, guocheng shi, huiwen chen
Journal: Circulation (2022)

Introduction: The prevalence of unrepaired congenital heart disease (CHD) before pregnancy is tremendously high, especially in developing countries. And their maternal outcomes haven’t been investigated at scale in a contemporaneous population. This study describes the maternal outcomes among pregnancies with unrepaired CHD. Methods: From 1993 to 2019, we nationally enrolled 2,220 CHD pregnancies from 7 tertiary centers. Patients were subdivided into two groups: pregnancies with unrepaired CHD and with repaired CHD. Maternal and offspring outcomes of completed pregnancies and their demographics, antenatal cardiac situation, and comorbidities were collected. To identify the risk factors for cardiac outcomes, univariate and multivariate analyses were performed through logistic regression. Results: Of 2,220 completed pregnancies with CHD, 1,272 women had unrepaired CHD. The main CHD diagnosis of unrepaired CHD patients was shunt lesion (64.54%). In parturients with unrepaired CHD, the incidence of mortality and heart failure were 1.73% and 14.94%, respectively. Pregnancies with unrepaired CHD had a significantly higher incidence of adverse maternal and offspring events than pregnancies with repaired CHD. Preterm delivery (22.56%) and low birth weight (21.15%) were the most common obstetric and offspring complications. Independent risk factors for maternal cardiac events included having a New York Heart Association functional class III-IV, elevated brain natriuretic peptide level, pulmonary hypertension, delayed first antenatal care visit, absence of strict antenatal supervision, and lack of multidisciplinary team management. Conclusions: In conclusion, pregnant women with unrepaired CHD were associated with significant morbidity and mortality. And they had significantly worse maternal and offspring outcomes than pregnant women with repaired CHD.
Abstract 11472: De-Escalation of Dual Antiplatelet Therapy in Elderly Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis
Authors: Tomohiro Fujisaki, Toshiki Kuno, Masao Iwagami, Yoshihisa Miyamoto, Hisato Takagi, Alexandros Briasoulis, Sidakpal Panaich, Azeem Latib, Shun Kohsaka
Journal: Circulation (2022)

Background: Recent randomized controlled trials (RCTs) have demonstrated the superiority of treating patients with acute coronary syndrome (ACS) with dual antiplatelet therapy (DAPT) uniform de-escalation strategy (i.e., switching from potent P2Y 12 inhibitors to clopidogrel one month after the event). However, it remains unclear if this strategy would be effective in elderly patients. We aimed to assess the efficacy of the available DAPT strategies, including the uniform de-escalation strategy, in ACS patients older than 65. Methods: We searched the PubMed, EMBASE, and Cochrane CENTRAL databases up to December 2021 for RCTs or subgroup analyses investigating DAPT strategies for elderly ACS patients (age ≥65 years) and conducted a network meta-analysis. The endpoint was net clinical benefit outcome, defined as a composite of major adverse cardiovascular events and bleeding. The P-score was used to rank the treatments. Results: Seven RCTs with 5,079 patients were included. The uniform de-escalation strategy was associated with a better net clinical benefit outcome (hazard ratio: 0.62; 95% confidence interval [0.41-0.92]) compared with DAPT using potent P2Y 12 inhibitors, and it was similarly effective compared with other DAPT strategies. There was no significant heterogeneity ( I 2 =0%; p =0.82) or inconsistency ( p =0.40). The uniform de-escalation strategy was ranked as the most effective strategy (by P score) superior to DAPT using clopidogrel or low-dose prasugrel. Conclusions: The uniform de-escalation strategy was an effective strategy for older ACS patients. Compared with conventional DAPT using potent P2Y 12 inhibitors, this strategy decreased the composite of major adverse cardiovascular events and bleeding events.
Abstract 11891: Adverse Childhood Experiences are Associated With Elevated Blood Pressure and Disturbed Sleep in the First Trimester of Pregnancy in Apparently Healthy, Young Adult Women
Authors: Nathaniel D Jenkins, Christopher E Kline, Bethany Barone Gibbs, Janet M Catov, Maisa Feghali, Mark K Santillan, Emily B Thomas, Melissa A Jones, Kara M Whitaker
Journal: Circulation (2022)

Introduction: Adverse childhood experiences (ACEs) are potentially traumatic psychosocial stressors that occur in early life, such as abuse, neglect, and household dysfunction. We hypothesize that ACEs are an underlying risk factor for disturbed sleep and hypertension in pregnancy, which is a major cause of maternal-fetal morbidity and mortality. Hypothesis: In young adult women, ACE exposure will be positively associated with first trimester systolic (SBP), diastolic blood pressure (DBP), and wakefulness after sleep onset (WASO), and inversely associated with sleep efficiency (SE). Further, ACE exposure will be associated with greater odds of first trimester elevated or stage 1 hypertension (ES1H). Methods: Data were obtained at 10-12 weeks of gestation from 142 pregnant women who were enrolled in an ongoing, clinical cohort study in Iowa City and Pittsburgh. Participants were 18-45 y of age, had a BMI &lt;40 kg/m 2 , and could not be taking medications or receiving treatment for sleep or cardiometabolic disorders such as chronic hypertension or diabetes. BP was assessed in accordance with AHA recommendations. Actigraphy was used to assess WASO and SE over ≥5 nights. ACE scores were log transformed and correlations were used to examine associations between ACE exposure and SBP, DBP, WASO and SE. Logistic regression was used to examine the association of ACE exposure with the probability of ES1H in an unadjusted model (model 1) and a model adjusted for age, race, ethnicity, BMI, and depressive symptoms (model 2). Results: 56% reported exposure to ≥1 ACE, and 28% reported exposure to ≥3. ACE exposure was positively related to SBP (r = 0.17, p = 0.04), DBP (r = 0.21, p = 0.01), and WASO (ρ = 0.21, p = 0.01), and negatively associated with SE (ρ = -0.22, p = 0.009). ACE exposure was associated with greater odds of first trimester ES1H in model 1 (OR = 2.73, 95% CI = 1.36 - 5.50; p = 0.005) and model 2 (OR = 2.44, 95% CI = 1.07 - 5.56; p = 0.03). Conclusions: ACEs represent an important risk factor for elevated BP and disturbed sleep in pregnancy. Large cohort studies are needed to understand the links among ACE exposure, sleep, resilience factors and hypertensive risk in pregnancy to provide information for developing targeted interventions to improve maternal-fetal cardiovascular health.
Abstract 11479: Adolescents Have Reduced Exercise Capacity After Heart Transplant
Authors: Nathan Markiewitz, Kathryn Stack, Meghan Lane-Fall, JING HUANG, Laura M Mercer-Rosa, Jonathan Mitchell, Matthew J O'Connor, Joseph Rossano, Stephen Paridon, Danielle Burstein, Jonathan B Edelson
Journal: Circulation (2022)

Introduction: There are limited data on exercise capacity and its determinants in pediatric heart transplant patients (HT). Methods: This single-center, retrospective cohort study of patients (&lt;18yo) includes subjects who received their index HT from 1990-2016 and completed a maximal effort cardiopulmonary exercise test (CPET) during adolescence (12-18yo). The primary outcome was maximum oxygen consumption (VO2). Secondary outcomes included anaerobic threshold (AT) and power consumption (PC). Outcomes were evaluated as percent predicted by sex and age. Wilcoxon rank-sum tests were used to test deviation from predicted exercise capacity. Linear regression models were used to assess association of clinical variables with CPET outcomes. Results: Our sample of 86 patients was 53% male (n=46), 68% White (n=53), with a median age at transplant of 10y (IQR [3-14]). The majority had a diagnosis of congenital heart disease (59%, n=51) and 21% (n=18) were supported with VAD prior to HT. The median age at EST was 17y (IQR 14.7, 17.6), mean time from OHT 7.1y (SD 5.3), and most patients were tested using cycle ergometry (87%, n=75). Max VO2 (median=26.3 ml/kg/min, 65% predicted), AT (median=17.5 ml/kg/min, 66% predicted) PC (median 1.8 w/kg, 56% predicted) were significantly lower than 100% predicted (p&lt;0.001 for all, Fig 1). After adjustment for age at transplant and time since transplant, increased BMI (b= -1.32 95% CI [-1.85, -0.79]) and decreased peak heart rate (HR) (b= 0.32 95% CI [0.19, 0.45]) predicted reduced max VO2. Ejection fraction, cardiac index, and pulmonary capillary wedge pressure measured on cardiac catheterization were not associated with max V02. Conclusions: Adolescents after HT demonstrate markedly reduced exercise capacity. While impaired chronotropy has been implicated in impaired exercise capacity in HT, the association of BMI is novel. The identification of this modifiable factor has important clinical implications for future interventions.
Abstract 11797: Totum-854 Anti-Oxidative Effect is Associated With Reduction of Blood Pressure and Tissue Remodeling in Spontaneous Hypertensive Rats
Authors: Doriane Ripoche, Arnaud Michaux, Vincent Pialoux, Marie Vallier, Cedric Langhi, Vivien Chavanelle, Florian Le Joubioux, Thierry MAUGARD, Yolanda F Otero, Sébastien PELTIER, Pascal Sirvent
Journal: Circulation (2022)

Introduction: Arterial Hypertension (AHT) is a major cause of premature death worldwide. Totum-854 (T-854) is a polyphenol-rich botanical composition dedicated to reduce the risk of developing AHT. We assessed its chronic effects on blood pressure in spontaneous hypertensive rats (SHR) and studied mechanisms of action involved. Methods: SHR rats received vehicle or T-854 (1000mg/kg) per os once a day for 8 weeks. Arterial pressure was recorded once a week with a radio-telemetry device (HD-S10, DSI). At the end of supplementation, rats were euthanized, and tissues were sampled out to analyze oxidative stress enzyme activities and gene expression profile. Media thickness was measured on aorta, embedded in paraffin and stained with Masson’s trichrome. w 1118 male drosophila were fed a diet containing paraquat (5mM) supplemented or not with 0,45% T-854. Mortality was recorded once a day. Results: In T-854-supplemented SHR rats, changes in SBP and DBP were significantly different in comparison to vehicle group (p&lt;0.05), with both parameters being maintained below vehicle values from the 2 nd week of supplementation to the end of the study. After 8 weeks of supplementation, antioxidant enzymes of supplemented rats exhibited increased SOD and catalase activity in plasma and myocardium, respectively. Moreover, the analysis of the expression of genes associated with oxidative stress showed a significant decrease in aortic Cybb and a significant increase in cardiac Sod1. T-854 antioxidant effects were associated with aorta and cardiac tissue remodeling, with an increase in aortic Col4a5 gene expression as well as a decrease in media thickness by 10% in supplemented rats and a decrease in cardiac MMP-2 gene expression. Finally, the antioxidant effects of T-854 in rats were confirmed in paraquat-fed drosophila, with a significant improvement of survival (p&lt;0.0001) and a median survival increased by 58% in comparison to paraquat diet alone. Conclusion: Chronic T-854 supplementation prevents AHT development in SHR rats. Remodeling of aortic and cardiac tissues is associated with an antioxidant effect that was confirmed in paraquat-fed drosophila. Taken together, T-854 appears as an efficient strategy to prevent AHT.
Abstract 11310: Neurologic, Renal, and Visceral Malperfusion are Associated With Increased Mortality in Acute Type A Dissection but Not Lower Extremity Malperfusion
Authors: Erik Schwarze, Abdul Kader Natour, Adam Chalek, Loay Kabbani, Kyle Miletic, Raed Alnajjar
Journal: Circulation (2022)

Introduction: The aim of this study was to evaluate malperfusion in patients presenting with acute type A dissection (ATAD) and correlate with mortality based on organ system involved. Methods: A registry of all patients who underwent ATAD repair at our tertiary referral center between 2002 and 2018 was retrospectively queried. Patients with type B aortic dissection and chronic type A aortic dissections (time from presentation &gt; 14 days) were excluded. Malperfusion syndromes at presentation including central nervous system (brain and spinal cord), visceral renal, and lower extremity (LE) were documented. Preoperative and intraoperative variables were analyzed, and post-operative outcomes were correlated with the malperfused organ system. Results: From 2002 to 2018, 378 patients underwent ATAD repair at our tertiary referral center. The average age was 57 years, 68% were male, and 51% were white. Approximately 70% of the cohort were transferred from an outside hospital. A total of 124 patients (33%) presented with malperfusion of at least one organ: 16% (N=62) LE, 8% (N=31) brain, 8% (N=30) renal, 3% (N=11) with visceral malperfusion, and 2% (N=8) with spinal cord malperfusion. On multivariate analysis, 30-day mortality was significantly increased in patients presenting with visceral ischemia (OR=3.7, P=0.04). The average follow-up was 2.3 years. Kaplan Meier survival curves showed a significant decrease in long term survival in patients presenting with brain (P=0.01), visceral (P=0.002), and renal ischemia (P&lt;0.001). No difference in short or long-term survival was seen in patients presenting with LE ischemia (P=0.28). Conclusions: In this review, 33% of ATAD patients presented with malperfusion of at least one organ system. Visceral malperfusion was associated with poor short-term survival, whereas CNS, renal, and visceral malperfusion had decreased long term survival. LE malperfusion had no association with short or long-term mortality.
Abstract 11503: Obesity-Related Biomarkers Associations With HFpEF and Exercise Intolerance
Authors: Mariana Ramirez Fernandez Del Castillo, Emily Lau, Matthew G Nayor, Dongyu Wang, Ravi V Shah, Jenna McNeill, Gregory Lewis, Rajeev Malhotra, Jennifer E Ho
Journal: Circulation (2022)

Background: Obesity and adiposity are associated with risk of heart failure with preserved ejection fraction (HFpEF), yet the role of adipokines and other obesity related pathways as contributors to HFpEF remains unclear. Objectives: We sought to examine the association of obesity and obesity related biomarkers including adipokines, inflammatory markers, and insulin resistance with HFpEF and specific cardiac and extracardiac organ reserve measures among patients who underwent CPET. Methods: We studied 509 consecutive patients with LVEF ≥ 50% and NYHA class II - III symptoms, who underwent clinically indicated CPET with invasive hemodynamic monitoring. Fasting blood samples at the time of CPET were used to assay obesity-related biomarkers, including leptin, adiponectin, resistin, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), glucose and insulin to estimate insulin resistance (HOMA-IR). We examined the association of biomarkers with physiologic HFpEF and exercise traits using multivariable regression models. Results: Among 509 patients (mean age 55 years, 61% women, 38% obese), 223 met hemodynamic criteria for HFpEF. Obesity was associated with more than 2-fold higher odds of HFpEF (OR 2.08, 95% CI 1.38-3.14). We found that higher levels of leptin, hsCRP and HOMA-IR were associated with greater odds of HFpEF (P ≤ 0.01, Figure 1). By contrast, resistin and adiponectin were not associated with HFpEF (P&gt;0.05). In secondary analyses, we observed associations of obesity related biomarkers with measures of impaired exercise capacity, such as lower peak VO 2 (P&lt;0.05), higher blood pressure response (leptin, HOMA-IR), and impaired heart rate response (hsCRP, HOMA-IR, IL-6, resistin). Conclusions: Obesity related biomarkers were associated with HFpEF and impaired exercise capacity. These findings highlight potential pathways underlying the association of obesity and cardiometabolic disease with development of HFpEF.